Goelet al.,Science 374 , eabm0829 (2021) 3 December 2021 6 of 17
B.1.1.7+ B.1.351+ B.1.617.2+InfectionRecoveredNaiveWT RBD++ mRNA Vaccine90.6 +/- 1.293.1 +/- 1.689.0 +/- 1.468.5 +/- 2.563 +/- 4.355.6 +/- 2.174 +/- 1.977 +/- 369.9 +/- 2.0Variant RBDsSSC-WB.1.1.7+ B.1.351+ B.1.617.2+ All Variant+0 2 4 60 2 4 60 2 4 60 2 4 6025507510002550751000255075100Months Post−Vaccine / Sero−Positivity% of WT RBD+Variant RBD BindingB.1.1.7+ B.1.351+ B.1.617.2+ All Variant+0255075100% of WT RBD+6 Months0.030
0.71Spike-BV421Nucleocapsid-BV6059.0034.456.2S2-BUV737NTD-BV786 54.3
B.1.351 RBD-PE68.1B.1.1.7 RBD-BV711WT RBD-BB51560.1B.1.617.2 RBD-APC69.6WT RBD-BB515SSC-WGated on Decoy- Gated on Spike+ NTD- S2-Memory B Cells (non-naive CD38lo/int)NTD+ RBD WT+ All Variant+ S2+0 2 4 6 0 2 4 6 0 2 4 6 0 2 4 61e−041e−031e−021e−011e+001e−041e−031e−021e−011e+001e−041e−031e−021e−011e+00Months Post−Vaccine / Sero−Positivity% of Total BSpike+ Memory B
NTD+ WT RBD+ S2+0 2 4 60 2 4 60 2 4 6020406080020406080020406080Months Post−Vaccine / Sero−Positivity% of Spike+Spike Immunodominancens
***
ns nsns
ns
ns**
nsns
ns
nsA BCEDSARS-CoV-2 Naive
N = 38SARS-CoV-2 Recovered
N = 10+ mRNA
VaccineVaccine
Baseline 1 month 3 months 6 months
SARS-CoV-2 Infection
N = 26Sero-
Positive
2 weeks 2 months 6 months
Mild
COVID-19K417N E484K N501Y
L452R T478KNTD RBD S2SARS-CoV-2 Spike ProteinB.1.1.7 (Alpha)
B.1.351 (Beta)
B.1.617.2 (Delta)Memory B CellsB.1.1.7+ B.1.351+ B.1.617.2+WT+
NTD+S2+Variants
Variant RBDs501Y 417N + 484K + 501Y 452R + 478KFH(SARS-CoV-2 Naive + mRNA)Binding to WT & B.1.1.7 & B.1.351 & B.1.617.2 = All Variant+Naive + mRNA Recovered + mRNA Infection
Pfizer ModernaG# of
Variants:
Cross-Binding to: B.1.1.7 B.1.351 B.1.617.26 Months
Infection0123Naive + mRNA0123Recovered + mRNA0123*** ns
**ns ns
nsNaiv
eRecoveredInfectio
nNaiv
eRecoveredInfectionNaiveRecoveredInfectio
n*** **ns 0.063 nsns *** *ns
ns ns
nsns ns
nsns nsnsns ns
0.066** ****0.068 ns
ns
* ns
ns* ns
** 0.0680.081ns ns
ns*** ****0.094** **ns+ mRNA Vaccine+ mRNAVaccin
e+ mRNA Vaccine**** ****0.056
****** *
***** ****ns
**** *** ********
****
ns ********* ns
******** ****
***** *ns
* *nsns *
*ns *
nsns ns
ns**** ************** *
* * **** *
*Fig. 3. Memory B cells induced by mRNA vaccination or infection are cross-
reactive to SARS-CoV-2 VOCs and increase in frequency over time.(Aand
B) Experimental design (A) and gating strategy (B) for quantifying the frequency and
phenotype of spike subunit and variant-specific memory B cells by flow cytometry.
Specific mutations in B.1.1.7, B.1.351, or B.1.617.2 variant RBDs are indicated.
(C) Frequencies of spike+NTD+, spike+WT RBD+, spike+all variant+(all variant
RBD binding), and spike+S2+memory B cells over time in PBMC samples from
vaccinated or convalescent individuals. Data are represented as a percentage of total
B cells. (D) Percent NTD+, RBD+,orS2+of total spike+memory B cells over time.
(E) Representative plots of variant RBD cross-binding gated on spike+WT RBD+cells
in vaccinated or convalescent individuals. Mean and standard error values at
the 6-month time point are indicated. (F) Percent B.1.1.7+, B.1.351+, B.1.617.2+,orall
variant+of WT RBD+memory B cells over time. (G) Boolean analysis of variant
cross-binding memory B cell populations in vaccinated, infected then vaccinated, or
infected-only individuals at 6 months after vaccination or seropositivity. Pie charts
indicate the fraction of WT RBD+memory B cells that cross-bind zero, one, two, or
three variant RBDs. Colored arcs indicate cross-binding to specific variants.
(H) Cross-sectional analysis of variant binding as a percentage of WT RBD+memory
B cells at 6 months after vaccination or seropositivity. For (C), (D), and (F), thick lines
indicate mean values, and thin lines represent individual subjects. Statistics were
calculated using paired [(C), (D), and (F)] or unpaired (H) nonparametric Wilcoxon
test with BH correction for multiple comparisons. Blue, red, and purple values
indicate comparisons within naïve, recovered, or infection-only groups, respectively.
*P< 0.05; **P< 0.01; ***P<0.001;****P< 0.0001; ns, not significant.RESEARCH | RESEARCH ARTICLE